Effects of sodium ursodeoxycholate, hyodeoxycholate and dehydrocholate on cholesterol and bile acid metabolism in rats.

Abstract

Effects of sodium ursodeoxycholate, hyodeoxycholate and dehydrocholate on serum and liver cholesterol levels, bile flow, biliary cholesterol, phospholipid and bile acid secretions, and fecal sterol and bile acid excretions were examined with Wistar strain male rats fed ordinary and 2% cholesterol supplemented diets. Dehydrocholate increased the liver cholesterol level, bile flow and biliary lipid secretion, but ursodeoxycholate and hyodeoxycholate did not. The serum cholesterol level was not changed by the treatments. Ursodeoxycholate and hyodeoxycholate increased their own secretion into the bile and decreased cholic acid secretion, while dehydrocholate increased deoxycholic acid and oxo bile acid secretion. Ursodeoxycholate increased but dehydrocholate decreased the fecal sterol excretion, and hyodeoxycholate caused no change. Dehydrocholate decreased the fecal coprostanol level. The total amounts of the fecal bile acids were similar in all the treated groups, but ursodeoxycholate increased lithocholic acid, α-, β- and ω-muricholic acids and ursodeoxycholic acid; hyodeoxycholate increased hyodeoxycholic acid, 3α, 7β, 12α-trihydroxy-5β-cholanoic acid and oxo bile acids; and dehydrocholate increased deoxycholic acid, cholic acid, ω-muricholic acid and oxo bile acids and decreased hyodeoxycholic acid. These data suggested that ursodeoxycholate was transformed into lithocholic and muricholic acids, and dehydrocholate into cholic and deoxycholic acids during the enterohepatic circulation, but hyodeoxycholate showed almost no change. Ursodeoxycholate and hyodeoxycholate caused neither accumulation of cholesterol in tissues nor increase in bile flow and biliary lipid secretion as well as chenodeoxycholate did. The biological effect of dehydrocholate was similar to that of cholate, and this was partially due to its conversion into cholic acid and deoxycholic acid.